Downregulation of PTPN18 can inhibit proliferation and metastasis and promote apoptosis of endometrial cancer

Abstract

Endometrial cancer is one of the chief culprits threatening women's lives. Although numerous epidemiological experiments have been carried out into the aetiology of endometrial cancer, the cause of the disease has been unclear up to now. In recent years, PTPN18, a member of the protein tyrosine phosphatases (PTP) family predicted to be tumour suppressors or oncogenes, has been confirmed to participate in the occurrence and progression of many cancers. Few studies, however, have explained the role in the endometrial cancer. So, it caught our attention to explore if PTPN18 participates in and plays a regulatory role in the proliferation, apoptosis, and metastasis of endometrial cancer. In our results, we found that PTPN18 was overexpressed in endometrial cancer tissue compared to paracancerous tissue by immunohistochemistry. Not only that, silencing of PTPN18 in endometrial cancer cell lines (HEC‐1‐A and HEC‐1‐B) can significantly impair proliferation detected by CCK8 assay and flow cytometry (FCM) analyses and inhibit the metastasis of endometrial cancer cells shown by the scratch test and the Transwell experiment. PTPN18 knockdown can promote the apoptosis of endometrial cancer. In addition, nude mice tumour formation assay confirmed the results in vivo. Although the exact function of PTPN18 in endometrial cancer is unclear, the targeted therapy drugs enhancing PTPN18 may be considered in the future treatment of endometrial carcinoma.

PTPN18 promotes colorectal cancer progression by regulating the c-MYC-CDK4 axis

“…Previous studies have demonstrated that PTPN18 is a tumor suppressor in breast cancer 29 and hepatocellular carcinoma, 30 while PTPN18 overexpression can promote the development of endometrial cancer. 23 In addition, different PTPs exert different functions in CRC. Specifically, PTPN4, 31 PTPN9, 32 and PTPRT 33 act as tumor suppressors in CRC, while PTPN2 34 can promote tumor development.…”

“… 20 , 21 , 22 However, recent studies have shown that PTPN18 knockdown can inhibit the proliferation of tumors and promote apoptosis in endometrial cancer. 23 …”

PTPN18 Stimulates the Development of Ovarian Cancer by Activating the PI3K/AKT Signaling

“…Protein tyrosine phosphatase nonreceptor type 18 (PTPN18) is the first discovered specific tyrosine phosphatase of human epidermal growth factor receptor 2 (HER2), which is closely linked to tumor development [13,14]. Protein tyrosine phosphatases influence cell growth and other cellular functions under external stimuli [13].…”

“…PTPN18 negatively regulates HER2 tyrosine kinase activity mainly through selectively dephosphorylating the tyrosine phosphorylation site of HER2, thereby effectively regulating cell function [13]. Previous evidence reported the expression of PTPN18 in kinds of tumor cell lines [13,14]. In addition, it is able to inhibit the progression of chronic myeloid leukemia and to influence functions of hematopoietic stem cells [13,14,16].…”

Roles of ferroptosis in urologic malignancies

“…Ferroptosis is a new type of tumor cell death, which plays an important role in multiple cancers [ 14 ]. PTPN18 is considered to serve as an oncogene in endometrial cancer, which promotes proliferation and metastasis of endometrial cancer cells [ 15 ]. Another study revealed that silencing of PTPN18 could induce ferroptosis by inhibiting GPX4 activity, leading to the suppression of endometrial cancer cell growth [ 16 ].…”